They synthesized the degrader 119 (MacPROTAC-1, Fig. 30) which induced more obvious affinity discrimination between BD1 and BD2 to the BET degrader MZ1 by adding a cyclizing linker and solved the co-crystal structure of VHL-119 (MacPROTAC-1)-BRD4 BD2.210 Compared with MZ1, the degrader 119 (MacPROTAC-1) showed similar degradation activity and inhibition of cell proliferation in BET-sensitive human prostate carcinoma 22RV1 cells, although the binding affinity to BRD4 decreased. Here, BRD4 is linked to prostate carcinoma.